The objective of the proposed research is to elucidate the mechanism of plasma cholesterol esterification by lecithin-cholesterol acyltransferase and the nature of the interaction between lecithin-cholesterol acyltransferase and high density lipoprotein, the primary substrate carrier. The specific objectives of the investigation include studies to: 1. Establish whether peviously reported inhibitions of the lecithin-cholesterol acyltransferase reaction are due to modification of the transferase enzyme or to modification of high density lipoprotein protein. 2. Determine if the inhibition of lecithin-cholesterol acyltransferase activity results in changes in the interaction between lecithin-cholesterol acyl transferase and high density lipoprotein. 3. Establish the nature and extent of involvement of specific high density lipoprotein protein functional groups which are found to participate in the interaction between the enzyme and high density lipoprotein. Both the enzyme and high density lipoprotein will be chemically modified with reagents having a high degree of specificity of reaction with specific amino acid residues of proteins. Effects of the modification on enzyme activity will be monitored. Then the effects of the mofidication on the interaction between the enzyme and lipoprotein will be investigated employing density gradient centrifugation and affinity chromatography.